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Sirppisolutauti ja sydän- ja verisuoniriski – punasolujen vaihtokoe (SCD-CARRE) (SCD-CARRE)

torstai 5. marraskuuta 2026 päivittänyt: Mark Gladwin, University of Pittsburgh

The SCD-CARRE trial is a Phase 3, prospective, randomized, multicenter, controlled, parallel two-arm study aimed to determine if automated exchange blood transfusion and standard of care administered to high mortality risk adult SCD patients reduces the total number of episodes of clinical worsening of SCD requiring acute health care encounters (non-elective infusion center/ER/hospital visits) or resulting in death over 12 months as compared with standard of care.

Tutkimuksen yleiskatsaus

Tila

Valmis

Ehdot

Interventio / Hoito

Yksityiskohtainen kuvaus

As patients with sickle cell disease (SCD) live to adulthood, the chronic impact of sustained hemolytic anemia and episodic vaso-occlusive events take their toll, with the progressive development of cardiopulmonary organ dysfunction. This culminates in the development of pulmonary hypertension, left ventricular diastolic heart disease, dysrhythmia, chronic kidney disease and sudden death, all major cardiovascular complications of SCD for which there are no approved or consensus therapies. The risk of having pulmonary hypertension and diastolic heart disease can be non-invasively assessed by laboratory tests (NT-proBNP) and Doppler-echocardiography (estimated pulmonary artery systolic pressure). A recent meta-analysis of approximately 6000 patients with SCD demonstrated that patients with elevated tricuspid regurgitant jet velocity (TRV), which is an Doppler-echocardiographic measurement that estimates the pulmonary artery systolic pressure, walked an estimated 30.4 meters less in a 6 minute walk test than those without elevated TRV, and elevated TRV was associated with high mortality (hazard ratio of 4.9). In two large registry cohorts of adult patients with SCD, the investigators found that approximately 20% of the adult SCD population have high values for both biomarkers, defined as a TRV ≥ 2.5 meters per second AND a NT-proBNP ≥ 160 pg/mL, and that the 12-month mortality rate is 7.9% in this group as compared to 0.5% in patients with normal TRV or NT-proBNP values, with a risk ratio for hospitalization of 1.6. This suggests that a simple screening profile of TRV and NT-proBNP can identify about 20% of patients with SCD at the highest risk of death and hospitalization.

Given the increased mortality and early loss of functional capacity associated with cardiovascular disease in SCD adults, it is important to test effective therapeutic interventions in such patients. Red blood cell transfusions are administered by either simple or exchange transfusion, the latter removes the patients blood and replaces it with transfused red blood cells. Exchange transfusions have proven effective for acute treatment of almost all SCD complications, including severe acute chest syndrome, stroke, splenic or hepatic sequestration, and multi-organ failure, and are also used chronically for stroke prevention and recurrent acute chest syndrome. In this study the investigators hypothesize that monthly exchange transfusion will limit disease progression, improve exercise capacity, and prevent interval episodes of vaso-occlusive painful crisis and the acute chest syndrome that acutely increases pulmonary pressures and cause right heart failure.

The investigators propose to perform a clinical trial to evaluate the effects of automated exchange blood transfusion on patient morbidity and mortality, compared to standard of care among 150 adult high risk SCD patients. The trial will leverage existing coordinating center infrastructure at the University of Pittsburgh and will involve 22 experienced clinical sites. Despite the safety and wide utilization of erythrocytapheresis in adult patients with SCD, there is no consensus or quality efficacy data on its use to improve outcomes in our aging high-risk SCD patients with progressive end-organ dysfunction.

Opintotyyppi

Interventio

Ilmoittautuminen (Todellinen)

173

Vaihe

  • Vaihe 3

Yhteystiedot ja paikat

Tässä osiossa on tutkimuksen suorittajien yhteystiedot ja tiedot siitä, missä tämä tutkimus suoritetaan.

Opiskelupaikat

  • Brasilia
      • Rio de Janeiro, Brasilia
        • Hemorio
  • Ranska
      • Créteil, Ranska
        • Kremlin-Bicêtre
      • Paris, Ranska
        • Henri Mondor Hopital
  • Yhdysvallat
    • Alabama
      • Tuscaloosa, Alabama, Yhdysvallat, 35401
        • University of Alabama
    • California
      • Oakland, California, Yhdysvallat, 94609
        • UCSF Benioff Children's Hospital Oakland
    • District of Columbia
      • Washington D.C., District of Columbia, Yhdysvallat, 20060
        • Howard University Center for Sickle Cell Disease
    • Georgia
      • Atlanta, Georgia, Yhdysvallat, 30322
        • Emory University
    • Illinois
      • Chicago, Illinois, Yhdysvallat, 60607
        • University of Illinois at Chicago
    • Maryland
      • Baltimore, Maryland, Yhdysvallat, 21201
        • University of Maryland
      • Baltimore, Maryland, Yhdysvallat, 21206
        • Johns Hopkins University
    • Massachusetts
      • Boston, Massachusetts, Yhdysvallat, 02118
        • Boston Medical Center
    • Missouri
      • St Louis, Missouri, Yhdysvallat, 63110
        • Washington University-St. Louis
    • New York
      • New York, New York, Yhdysvallat, 10029
        • Icahn School of Medicine at Mount Sinai
      • New York, New York, Yhdysvallat, 10461
        • Montefiore Medical Center
    • North Carolina
      • Chapel Hill, North Carolina, Yhdysvallat, 27599
        • University of North Carolina at Chapel Hill
      • Charlotte, North Carolina, Yhdysvallat, 28204
        • Atrium Health
      • Durham, North Carolina, Yhdysvallat, 27708
        • Duke University
      • Greenville, North Carolina, Yhdysvallat, 27834
        • East Carolina University
    • Ohio
      • Cleveland, Ohio, Yhdysvallat, 44106
        • University Hospitals Cleveland Medical Center
      • Columbus, Ohio, Yhdysvallat, 43210
        • Ohio State University
    • Pennsylvania
      • Pittsburgh, Pennsylvania, Yhdysvallat, 15232
        • University of Pittsburgh Medical Center
    • Texas
      • Houston, Texas, Yhdysvallat, 77030
        • University of Texas Health Science Center at Houston
    • Virginia
      • Richmond, Virginia, Yhdysvallat, 23284
        • Virginia Commonwealth University

Osallistumiskriteerit

Tutkijat etsivät ihmisiä, jotka sopivat tiettyyn kuvaukseen, jota kutsutaan kelpoisuuskriteereiksi. Joitakin esimerkkejä näistä kriteereistä ovat henkilön yleinen terveydentila tai aiemmat hoidot.

Kelpoisuusvaatimukset

Opintokelpoiset iät

18 vuotta ja vanhemmat (Aikuinen, Vanhempi Aikuinen)

Hyväksyy terveitä vapaaehtoisia

Ei

Sukupuolet, jotka voivat opiskella

Kaikki

Kuvaus

Inclusion Criteria:

  • Age 18 years or older

  • Diagnosis of SCD: homozygous sickle cell disease, hemoglobin-SC, Sβ-thalassemia, hemoglobin-SO or hemoglobin-SD.

  • Patients not on a chronic exchange transfusion program for at least 60 days.

  • If patients are on a SCD drug (e.g. hydroxyurea, glutamine, or P-selectin inhibitors), the doses must be stable for at least 60 days prior to randomization. At the time of randomization, participants must be off Oxbryta for at least 30 days.

  • Any one of the following vasculopathy biomarker clinical results (a, b, c, d or e) measured in the last 24 months before randomization that indicates a high-risk patient:

    1. Both a TRV 2.5- <3.0 m/sec and NT-proBNP plasma level ≥ 160 pg/mL,
    2. TRV ≥ 3.0 m/sec,
    3. Both a mean pulmonary artery pressure (PAP) by right heart catheterization 20-24 mmHg and NT-proBNP plasma level ≥ 160 pg/mL,
    4. Mean PAP by right heart catheterization ≥ 25 mmHg,
    5. Chronic kidney disease (CKD) due to SCD with abnormal measures on 2 separate occasions as defined by: macroalbuminuria (albumin to creatinine ratio (ACR) >300 mg/g) or proteinuria (protein to creatinine ratio >30 mg/mmol), or estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2. (It is recommended that local laboratories use Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] equation without ethnic factors when estimating and reporting GFR).

Clinical results of these biomarkers measured locally at sites within 24 months prior to randomization are acceptable to determine eligibility. TRV, PAP, NT-proBNP, albumin to creatinine ratio, protein to creatinine ratio, or eGFR values must be measured in a steady state (defined as measured ≥ 14 days since an acute care pain event) on different days.

vi. Written informed consent obtained from patient to participate in the trial.

Exclusion Criteria:

  • RBC alloimmunization resulting in inability of blood bank to obtain compatible components for chronic exchange transfusions
  • Previous history of hyper-hemolysis syndrome
  • Previous history of severe transfusion reaction resulting in renal failure or due to serious complications such as hypotension or respiratory distress
  • More than 10 vaso-occlusive episodes in the past 12 months requiring admission to a hospital to receive treatment.
  • Religious objection to receiving blood transfusion
  • Diagnosis of ischemic stroke within the past 6 months
  • Clinical evidence of liver failure or advanced cirrhosis or any co-existing medical condition that in the Investigator's judgement will substantially increase the risk associated with the patient's participation in the trial
  • Women of childbearing potential who have a positive pregnancy test at baseline

Opintosuunnitelma

Tässä osiossa on tietoja tutkimussuunnitelmasta, mukaan lukien kuinka tutkimus on suunniteltu ja mitä tutkimuksella mitataan.

Miten tutkimus on suunniteltu?

Suunnittelun yksityiskohdat

  • Ensisijainen käyttötarkoitus: Hoito
  • Jako: Satunnaistettu
  • Inventiomalli: Rinnakkaistehtävä
  • Naamiointi: Yksittäinen

Aseet ja interventiot

Osallistujaryhmä / Arm
Interventio / Hoito
Kokeellinen: Exchange transfusion plus standard of care

Randomized to standard of care and automated exchange blood transfusion every 3-6 weeks for 12 months.
Biologinen: Red Blood Cell

Red blood cell exchange transfusions will be performed every 3-6 weeks to maintain a target post-transfusion hemoglobin S level of <20% and a pre-transfusion hemoglobin S of <30%.

Muut nimet:
  • Punasolut (RBC)
Muut: Standard of care

NHLBI/ASH/ATS Expert Panel recommended guidelines
Active Comparator: Standard of care

Randomized to standard of care
Muut: Standard of care

NHLBI/ASH/ATS Expert Panel recommended guidelines

Mitä tutkimuksessa mitataan?

Ensisijaiset tulostoimenpiteet

Tulosmittaus
Toimenpiteen kuvaus
Aikaikkuna
Episodes of clinical worsening
Aikaikkuna: 13 months

The efficacy of the intervention will be measured by comparing the total number of episodes of clinical worsening of SCD requiring acute health care encounters (non-elective infusion center/ER/Hospital visits) or resulting in death over 13 months between groups.
13 months

Toissijaiset tulostoimenpiteet

Tulosmittaus
Toimenpiteen kuvaus
Aikaikkuna
Acute healthcare event
Aikaikkuna: 13 months

A 6-level prioritized rank-based outcome: 1.No death or SCD-related acute health care encounters (SCDAcuteE) within (w/in) 13 months (m) of randomization; 2. Had SCDAcuteE but NO major complications (acute kidney injury (AKI), acute chest syndrome (ACS), cor pulmonale, stroke, liver failure) associated with an SCDAcuteE nor death w/in 13 m of randomization; 3. Had 1 major complication (AKI, ACS, cor pulmonale, stroke, or liver failure) associated with an SCDAcuteE but not death w/in 13 m of randomization; 4. Had 2 major complications (AKI, ACS, cor pulmonale, stroke, or liver failure) associated with SCDAcuteE but not death w/in 13 m of randomization; 5. Had ≥ 3 major complications (AKI, ACS, cor pulmonale, stroke, or liver failure) associated with SCDAcuteE but not death w/in 13 m of randomization; 6.Death w/in 13 m of randomization. If the same complication reoccurs, occurrences will be counted as separate complications if the acute health care encounters are separated by ≥7 days.
13 months
Twelve-month survival
Aikaikkuna: 13 months

Survival over thirteen-month period will be analyzed and compared between the group receiving the intervention and the group receiving care routinely provided for sickle cell patients based on the NHLBI guidelines.
13 months
Survival free of acute healthcare encounters
Aikaikkuna: 13 months

Survival free of acute health care encounters over 13 months.
13 months
Total number of acute health care encounters
Aikaikkuna: 13 months

The total number of acute health care encounters (non-elective infusion center/ER/Hospital visits) with evidence of cor pulmonale (physical exam findings, NT-proBNP increase plus echocardiographic evidence of worsening right heart function).
13 months
Measures of exercise capacity - 6 minute walk distance
Aikaikkuna: 4, 8, and 12 months

Measures of exercise capacity assessed at 4, 8 and 12 months by the distance walked in the six minute walk distance assessment
4, 8, and 12 months
Measures of exercise capacity - outpatient activity
Aikaikkuna: 4, 8, and 12 months

Measures of exercise capacity assessed at 4, 8 and 12 months by the distance walked in a 7 day in the outpatient setting.
4, 8, and 12 months
Cardiovascular risk
Aikaikkuna: 12 months

Established cardiovascular risk biomarkers and indices are combined to help the investigators form an opinion about cardiovascular risks. The following will be measured: NT-proBNP, QT prolongation, systemic pulse pressure, albuminuria, estimated GFR and CKD progression Kidney Disease Improving Global Outcomes (KDIGO) CKD Work Group criteria.
12 months
Development of new leg ulcers
Aikaikkuna: 4, 8 and 12 months

Participants will be assessed for development of new leg ulcers at each physical exam.
4, 8 and 12 months
Measures of exercise capacity - WHO Classification
Aikaikkuna: 4, 8 and 12 months

WHO functional status severity will be measured assessing by looking at limitation of usual physical activity from I (no limitation in usual physical activity) to Class IV (inability to perform any physical activity at rest)
4, 8 and 12 months
Nocturnal desaturation
Aikaikkuna: 4, 8 and 12 months

Nocturnal desaturation will measured using a wearable device to measure blood oxygen saturation for 7 nights at home.
4, 8 and 12 months
SCD specific patient reported outcomes - Pain
Aikaikkuna: 4, 8 and 12 months

SCD specific patient reported outcomes as measured by self-reported pain
4, 8 and 12 months
SCD specific patient reported outcomes -Quality of Life modified PROMIS scale
Aikaikkuna: 4, 8 and 12 months

SCD specific patient reported outcomes as measured by a modified version of health related quality of life questionnaire from PROMIS QoL measure
4, 8 and 12 months
SCD specific patient reported outcomes -Quality of Life modified ASCQ-Me scale
Aikaikkuna: 4, 8 and 12 months

SCD specific patient reported outcomes as measured by a modified version of health related quality of life questionnaire from ASCQ-Me QoL measure
4, 8 and 12 months
Cardiovascular function by echocardiography - TRV
Aikaikkuna: 4, 8 and 12 months

Cardiovascular function measures from echocardiography assessed at 4, 8 and 12 months: echocardiographic measures of tricuspid regurgitant jet velocity in m/s.
4, 8 and 12 months
Cardiovascular function by echocardiography - diastolic left heart function
Aikaikkuna: 4, 8 and 12 months

Diastolic left heart function measured by E/A ratio, E/Em ratio, and deceleration times will be assessed by echocardiography.
4, 8 and 12 months
Cardiovascular function by echocardiography - systolic right heart function
Aikaikkuna: 4, 8 and 12 months

Systolic right heart health will be measured by assessing tricuspid annular plane systolic excursion (TAPSE), right ventricular size and contractility from echocardiography of the heart.
4, 8 and 12 months
Total number of acute health care encounters
Aikaikkuna: 13 months

The number of acute health care encounters (non-elective infusion center/ER/Hospital visits) with at least one major complication.
13 months

Yhteistyökumppanit ja tutkijat

Täältä löydät tähän tutkimukseen osallistuvat ihmiset ja organisaatiot.

Sponsori

University of Pittsburgh

Yhteistyökumppanit

National Heart, Lung, and Blood Institute (NHLBI)

Tutkijat

  • Päätutkija: Maria Brooks, PhD, University of Pittsburgh
  • Opintojen puheenjohtaja: Mark Gladwin, MD, University of Maryland
  • Päätutkija: Darrell Triulzi, MD, University of Pittsburgh

Julkaisuja ja hyödyllisiä linkkejä

Tutkimusta koskevien tietojen syöttämisestä vastaava henkilö toimittaa nämä julkaisut vapaaehtoisesti. Nämä voivat koskea mitä tahansa tutkimukseen liittyvää.

Yleiset julkaisut

Opintojen ennätyspäivät

Nämä päivämäärät seuraavat ClinicalTrials.gov-sivustolle lähetettyjen tutkimustietueiden ja yhteenvetojen edistymistä. National Library of Medicine (NLM) tarkistaa tutkimustiedot ja raportoidut tulokset varmistaakseen, että ne täyttävät tietyt laadunvalvontastandardit, ennen kuin ne julkaistaan ​​julkisella verkkosivustolla.

Opi tärkeimmät päivämäärät

Opiskelun aloitus (Todellinen)

Keskiviikko 26. helmikuuta 2020

Ensisijainen valmistuminen (Todellinen)

Maanantai 11. toukokuuta 2026

Opintojen valmistuminen (Todellinen)

Lauantai 31. lokakuuta 2026

Opintoihin ilmoittautumispäivät

Ensimmäinen lähetetty

Maanantai 26. elokuuta 2019

Ensimmäinen toimitettu, joka täytti QC-kriteerit

Maanantai 9. syyskuuta 2019

Ensimmäinen Lähetetty (Todellinen)

Tiistai 10. syyskuuta 2019

Tutkimustietojen päivitykset

Viimeisin päivitys julkaistu (Todellinen)

Tiistai 10. marraskuuta 2026

Viimeisin lähetetty päivitys, joka täytti QC-kriteerit

Torstai 5. marraskuuta 2026

Viimeksi vahvistettu

Sunnuntai 1. marraskuuta 2026

Lisää tietoa

Tähän tutkimukseen liittyvät termit

Muita asiaankuuluvia MeSH-ehtoja

Muut tutkimustunnusnumerot

  • STUDY20110362
  • UG3HL143192 (Yhdysvaltain NIH-apuraha/sopimus)

Yksittäisten osallistujien tietojen suunnitelma (IPD)

Aiotko jakaa yksittäisten osallistujien tietoja (IPD)?

JOO

IPD-suunnitelman kuvaus

Results from research conducted under this project will be shared in several ways. Manuscripts will be submitted for publication in high-quality peer-reviewed journals, following the NIH Public Access Policy guidelines. Findings will be presented at relevant national conferences, public lectures, scientific institutions and meetings. The timeline for participant recruitment, data collection and analysis will foster publication, facilitated by the investigators' Publications Committee, of critically important and clinically relevant data throughout the trial. The study datasets will be archived and made available to qualified individuals after a period of exclusive use by the SCD-CARRE trial research team and after publication of the primary manuscripts, following NIH guidelines.

IPD-jaon aikakehys

At the end of the trial, study de-identified datasets will be submitted for permanent archive in the NHLBI BioLINCC repository. The trial will also produce deliverables that will be freely available to the sickle cell community including a description of the protocol for automated red blood cell exchange transfusion.

IPD-jaon käyttöoikeuskriteerit

All publications based on the SCD-CARRE trial will adhere to the NIH Public Access Policy (Notice NOT-OD-08-033). All study data will be de-identified. At the end of the trial, study de-identified datasets will be submitted for permanent archive in the NHLBI BioLINCC repository.

The investigators also will work closely with regional and National SCD Foundations to promote recruitment for this study and communicate our results.

IPD-jakamista tukeva tietotyyppi

  • CSR

Lääke- ja laitetiedot, tutkimusasiakirjat

Tutkii yhdysvaltalaista FDA sääntelemää lääkevalmistetta

Joo

Tutkii yhdysvaltalaista FDA sääntelemää laitetuotetta

Ei

Yhdysvalloissa valmistettu ja sieltä viety tuote

Ei

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